Taste Cells of the Type III Employ CASR to Maintain Steady Serotonin Exocytosis at Variable Ca in the Extracellular Medium.

Type III taste cells are the only taste bud cells which express voltage-gated (VG) Ca channels and employ Ca-dependent exocytosis to release neurotransmitters, particularly serotonin. The taste bud is a tightly packed cell population, wherein extracellular Ca is expected to fluctuate markedly due to the electrical activity of taste cells. It is currently unclear whether the Ca entry-driven synapse in type III cells could be reliable enough at unsteady extracellular Ca. Here we assayed depolarization-induced Ca signals and associated serotonin release in isolated type III cells at varied extracellular Ca. It turned out that the same depolarizing stimulus elicited invariant Ca signals in type III cells irrespective of bath Ca varied within 0.5-5 mM. The serotonin release from type III cells was assayed with the biosensor approach by using HEK-293 cells co-expressing the recombinant 5-HT4 receptor and genetically encoded cAMP sensor Pink Flamindo. Consistently with the weak Ca dependence of intracellular Ca transients produced by VG Ca entry, depolarization-triggered serotonin secretion varied negligibly with bath Ca. The evidence implicated the extracellular Ca-sensing receptor in mediating the negative feedback mechanism that regulates VG Ca entry and levels off serotonin release in type III cells at deviating Ca in the extracellular medium.